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Yak Genome Sequence Provides Insights into High-Altitude Adaptation

An international team, led by Lanzhou University, and including BGI, the world's largest genomics organization, the Institute of Kunming Zoology, the Chinese Academy of Sciences, as well as twelve other institutes, has completed the genomic sequence and analyses of a female domestic yak, which provides important insights into understanding mammalian divergence and adaptation at high altitude. This study was published online on July 1, 2012 in Nature Genetics. As an iconic symbol of Tibet and of high altitude, the yak (Bos grunniens) is the most important domesticated species for Tibetans living at high altitude in China's Qinghai Province, which could provide meat and other basic resources, such as milk, transportation, dried dung for fuel, and hides for tented accommodation. Yaks have many anatomical and physiological traits that enable them to live at high altitude, including high metabolism, acute senses, impressive foraging ability, enlarged hearts and lungs, and a lack of blood vessel constriction in the lungs when faced with relatively low oxygen conditions. In the study, researchers sequenced the genome of a female domestic yak using high-throughput sequencing technology. The genomic data yielded a 2,657-Mb draft yak genome assembly that had 65-fold coverage. The researchers also conducted transcriptome sequencing on RNA samples derived from fresh heart, liver, brain, stomach, and lung tissues collected from the same yak. Based on the transcriptome data, researchers estimated that the yak genome contains 22,282 protein-coding genes and 2.2 million heterozygous SNPs. In order to understand evolutionary adaptation of yak to the high altitude, the team conducted comparative genomic analyses between yak and cattle, a closely related animal that typically lives at much lower altitudes. Although the yak and cattle were estimated to have diverged around 4.9 million years ago, many of the yak and cattle genes have remained very similar, with the two animals sharing 45 percent protein identity and 99.5 percent protein similarity. However, the researchers identified distinct gene expansions related to sensory perception and energy metabolism-related in yak. In addition, researchers also found an enrichment of protein domains related to the extracellular environment and hypoxic stress. Especially, they found the orthologous genes in yak related to hypoxia and nutrition metabolism had undergone positive selection and rapid evolution. For example, they found three genes that may play important roles in regulating the body's response to hypoxia, or oxygen deprivation, at high altitudes, and five genes that were related to the optimization of the energy from the poor foods in the extreme plateau. Researchers said that the study on high-altitude adaptation may help to improve current understanding, treatment, and prevention of altitude sickness and other hypoxia-related diseases in humans. Moreover, the yak genome provided a valuable resource for accelerating the genetic improvement of milk and meat production of this important animal. [Press release] [Nature Genetics abstract]